A Phase 2, Placebo-Controlled Study To Evaluate The Efficacy And Safety Of PF-00489791 In Patients With Type 2 Diabetes And Overt Nephropathy
- Registration Number
- NCT01200394
- Lead Sponsor
- Pfizer
- Brief Summary
PF-00489791 is an inhibitor of phosphodiesterase type 5. Our hypothesis is that PF-00489791 will enhance the relaxation of blood vessels within the kidney and so reduce blood pressure, improving renal function.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 256
- Male or female subjects greater than or equal to 18 years. Female subjects must be of non-child bearing potential.
- Clinical diagnosis of type 2 diabetes together with stages 3a, 3b or 4 CKD, based on an eGFR of 25-59 mL/min/1.73m2.
- Evidence of persistent, overt albuminuria; defined as a UACR greater than or equal to 300 mg/g (greater than or equal to 33.9 mg/mmol) for greater than 3 months.
- Subjects with CKD resulting from type 1 diabetes or non-diabetic CKD.
- Subjects with poorly controlled diabetes mellitus, defined as HbA1C >9%.
- Subjects on combination ACE inhibitor/ARB therapy.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo Placebo - PF-00489791 PF-00489791 -
- Primary Outcome Measures
Name Time Method Change From Baseline in Urinary Albumin Creatinine Ratio (UACR) at Week 12 Baseline, Week 12 (Day 5, 6, 7) UACR was ratio of albumin measured in urine (milligram) to creatinine measured in urine (millimole), reported in units milligram per millimole (mg/mmol). A decrease in UACR may be associated with improved renal and cardiovascular function. The mean values of the 3 consecutive first morning void urine samples (obtained 2 days prior to \[Day 5, 6 of Week 12\], and with last sample collected on the morning of scheduled clinic visit \[Day 7 of Week 12\]) were used to determine UACR at the scheduled clinic visit. The mean values of the 3 consecutive first morning void urine samples obtained at screening were used to determine baseline UACR.
- Secondary Outcome Measures
Name Time Method Change From Baseline in Urinary Albumin Creatinine Ratio (UACR) at Week 3, 6 and 16 Baseline, Week 3 (Day 5, 6, 7), Week 6 (Day 5, 6, 7), Week 16 (Day 5, 6, 7) UACR was ratio of albumin measured in urine (milligram) to creatinine measured in urine (millimole), reported in units mg/mmol. A decrease in UACR may be associated with improved renal and cardiovascular function. The mean values of the 3 consecutive first morning void urine samples (obtained 2 days prior to \[Day 5, 6 of specified Week\], and with last sample collected on the morning of scheduled clinic visit \[Day 7 of specified Week\]) were used to determine UACR at the scheduled clinic visit. The mean values of the 3 consecutive first morning void urine samples obtained at screening were used to determine baseline UACR.
Change From Baseline in Urinary Protein Creatinine Ratio (UPCR) at Week 3, 6, 12, and 16 Baseline, Week 3 (Day 5, 6, 7), Week 6 (Day 5, 6, 7), Week 12 (Day 5, 6, 7), Week 16 (Day 5, 6, 7) UPCR is a ratio between two measured substances in urine: milligram of protein per millimole (mmol) of creatinine, reported in units mg/mmol. A decrease in UPCR may be associated with improved renal and cardiovascular function. The mean values of the 3 consecutive first morning void urine samples (obtained 2 days prior to \[Day 5, 6 of Week 3, 6, 12, 16\], and with last sample collected on the morning of scheduled clinic visit \[Day 7 of Week 3, 6, 12, 16\]) were used to determine UPCR at the scheduled clinic visit. The mean values of the 3 consecutive first morning void urine samples obtained at screening were used to determine baseline UPCR.
Change From Baseline in Serum Creatinine Concentration at Week 3, 6, 12, and 16 Baseline, Week 3, 6, 12, 16 (follow-up) Serum creatinine concentration was used as a marker of renal function. Baseline serum creatinine concentration was determined predose at Week 0 (Day 1).
Change From Baseline in Estimated Glomerular Filtration Rate (eGFR) at Week 3, 6, 12, and 16 Baseline, Week 3, 6, 12, 16 (follow-up) The eGFR was calculated using 4 variable formula developed by the modification of diet in renal disease (MDRD) study group. The 4 variables needed to estimate glomerular filtration rate (GFR) using this formula were serum creatinine concentration (sCr), age, sex (for females, eGFR was multiplied by 0.742) and ethnic origin (for African-Caribbean people only, eGFR was multiplied by 1.212). Thus eGFR in milliliter per minute per 1.73 square meter (mL/min/1.73 m\^2) = 175\*(sCr/88.4)\^-1.154\*(Age)\^-0.203\*(0.742 if female)\*(1.212 if African-Caribbean). Baseline eGFR was determined predose at Week 0 (Day 1).
Systolic, Diastolic and Mean Blood Pressure at Week 0, 3, 6, 12, and 16 Week 0, 3, 6, 12, 16 (follow-up) Systolic blood pressure (SBP) is the blood pressure (pressure exerted by circulating blood on the walls of blood vessels) when heart is contracting; it is the maximum arterial pressure during contraction of left ventricle of heart. diastolic blood pressure (DBP) is the blood pressure (pressure exerted by circulating blood on the walls of blood vessels) when heart is relaxing; it is the minimum arterial pressure during relaxation and dilation of ventricles of heart. Mean blood pressure (MBP) = diastolic blood pressure + (\[systolic blood pressure - diastolic blood pressure\]/3). After a minimum of 5 minutes of rest, supine BP was measured with the participant's arm supported at the level of the heart.
Change From Baseline in Urine Transforming Growth Factor (TGF) Beta-1 Concentration at Week 3, 6, 12, and 16 Baseline, Week 3, 6, 12, 16 (follow-up) TGF Beta-1 is a major fibrogenic growth factor implicated in the pathogenesis of renal scarring. It is overexpressed in the diabetic kidney where it may promote matrix accumulation. Baseline TGF Beta-1 concentration was determined predose at Week 0 (Day 1).
Change From Baseline in Serum High Sensitivity C-Reactive Protein (Hs-CRP) Concentration at Week 12 and 16 Baseline, Week 12, 16 (follow-up) The CRP is an acute phase reactant which is virtually absent from the blood serum of healthy persons but rapidly appears in blood and body fluids in response to injurious stimuli. Baseline hs-CRP was determined predose at Week 0 (Day 1).
Change From Baseline in Serum Cystatin-C Concentration at Week 12 and 16 Baseline, Week 12, 16 (follow-up) Cystatin C is produced by all nucleated cells at a constant rate and is freely filtered at the glomerulus. The blood concentration of cystatin C depends almost entirely on the GFR and is not substantially affected by diet, nutritional status or inflammatory disease. Serum cystatin C had been proposed as an endogenous marker of GFR in participant with chronic kidney disease (CKD) than sCr. Baseline serum cystatin C was determined predose at Week 0 (Day 1).
Plasma Concentration Versus Time Summary of PF-00489791 Pre-dose at Day 1 of Week 0, 3, 6 and 12; 4 hours post-dose on Day 1 of Week 0, 3 and 6
Trial Locations
- Locations (156)
North America Research Institute
🇺🇸Azusa, California, United States
California Kidney Specialists
🇺🇸San Dimas, California, United States
Research Across America
🇺🇸Houston, Texas, United States
North American Research Institute / California Kidney Specialist
🇺🇸Azusa, California, United States
Northwest Louisiana Nephrology
🇺🇸Shreveport, Louisiana, United States
Lincoln Nephrology and Hypertension
🇺🇸Lincoln, Nebraska, United States
Houston Nephrology Research
🇺🇸Houston, Texas, United States
N/A - formerly with Entralogix SMO
🇨🇦Toronto, Ontario, Canada
P. D. Hinduja National Hospital and Medical Research Centre
🇮🇳Mumbai, Maharashtra, India
Deenanath Mangeshkar Hospital & Research Centre
🇮🇳Pune, Maharashtra, India
Diabetes Care and Research Centre
🇮🇳Pune, Maharashtra, India
KE.M Hospital Research Centre
🇮🇳Pune, Maharashtra, India
Saadat Ansari Internal Medicine
🇺🇸Huntsville, Alabama, United States
Southwest Clinical Research Institute, LLC
🇺🇸Tempe, Arizona, United States
ASA Clinical Research, LLC
🇺🇸Jupiter, Florida, United States
Lakeview Medical Research
🇺🇸Summerfield, Florida, United States
Chicago Clinical Research Institute, Inc.
🇺🇸Chicago, Illinois, United States
Four Rivers Clinical Research, Inc.
🇺🇸Paducah, Kentucky, United States
Crescent City Clinical Research Center
🇺🇸Metairie, Louisiana, United States
Biolab Research, LLC
🇺🇸Rockville, Maryland, United States
Alzohaili Medical Consultants
🇺🇸Dearborn, Michigan, United States
Apex Medical Research, AMR, Inc.
🇺🇸Flint, Michigan, United States
Apex Medical Research, MI, Inc.
🇺🇸Flint, Michigan, United States
Columbia Nephrology Associates, PA
🇺🇸Columbia, South Carolina, United States
Carolina Nephrology, PA
🇺🇸Greenville, South Carolina, United States
Palmetto Nephrology, PA
🇺🇸Orangeburg, South Carolina, United States
South Carolina Nephrology & Hypertension Ctr, Inc
🇺🇸Orangeburg, South Carolina, United States
South Carolina Nephrology and Hypertension Center
🇺🇸Orangeburg, South Carolina, United States
Renal Research Practice
🇦🇺Gosford, New South Wales, Australia
John Hunter Hospital
🇦🇺Newcastle, New South Wales, Australia
Department of Nephrology
🇦🇺New Lambton, Newcastle, Australia
Pharmacy Department
🇦🇺New Lambton, Newcastle, Australia
Melbourne Renal Research Group
🇦🇺Reservoir, Victoria, Australia
University of Alberta Hospital
🇨🇦Edmonton, Alberta, Canada
Entralogix Clinical Research Inc.
🇨🇦Oakville, Ontario, Canada
London Health Sciences Centre
🇨🇦London, Ontario, Canada
Sunnybrook Health Sciences Center
🇨🇦Toronto, Ontario, Canada
Saskatoon Nephrology Group, Nurses Redisence
🇨🇦Saskatoon, Saskatchewan, Canada
Saskatoon Nephrology Group, Nurses Residence
🇨🇦Saskatoon, Saskatchewan, Canada
Gujarat Kidney Foundation
🇮🇳Ahmedabad, Gujarat, India
Apollo Hospitals
🇮🇳Hyderabad, Andhra Pradesh, India
Pfizer Centre
🇮🇳Mumbai, Maharashtra, India
Jehangir Clinical Development Centre Pvt. Ltd.
🇮🇳Pune, Maharashtra, India
Pharmacy
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Seoul National University Hospital
🇰🇷Seoul, Korea, Republic of
Samsung Medical Center,Sungkyunkwan Univ School of Medicine
🇰🇷Seoul, Korea, Republic of
Unit Hemodialisis, Hospital Serdang
🇲🇾Kajang, Selangor, Malaysia
Nephrology Clinic, Queen Elizabeth Hospital
🇲🇾Kota Kinabalu, Sabah, Malaysia
Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran (INCMNSZ)
🇲🇽Tlalpan, Mexico CITY, Mexico
NZOZ "DIAGNOMED" S.C., Poradnia Nefrologiczna
🇵🇱Bielsko-Biala, Poland
NZOZ PS "Medica"
🇵🇱Lublin, Poland
Centrum Medyczne "Osteomed" NZOZ, Lecznica Specjalistow
🇵🇱Warszawa, Poland
SPZOZ Akademicki Szpital Kliniczny im. J. Mikulicza - Radeckiego
🇵🇱Wroclaw, Poland
Centrum Medyczne "Osteomed"
🇵🇱Warszawa, Poland
Clinic for Nephrology, Military Medical Academy
🇷🇸Belgrade, Serbia
Clinical Hospital Center Zvezdara
🇷🇸Belgrade, Serbia
Clinic for Endocrinology, Clinical Center Nis
🇷🇸Nis, Serbia
FNsP Bratislava, Nemocnica Stare Mesto
🇸🇰Bratislava, Slovakia
Wits Clinical research
🇿🇦Johannesburg, Gauteng- South Africa, South Africa
Nemocnice s poliklinikami n.o.
🇸🇰Levice, Slovakia
Vseobecna nemocnica Rimavska Sobota
🇸🇰Rimavska Sobota, Slovakia
Worthwhile Clinical Trials (WWCT), Lake View Hospital
🇿🇦Benoni, Gauteng, South Africa
Division of Nephrology and Hypertension, E13 Renal Unit
🇿🇦Cape Town, South Africa
Dr. George Mukhari Hospital -University of Limpopo
🇿🇦Pretoria, Gauteng, South Africa
Centre for Diabetes and Endocrinology
🇿🇦Houghton, Johannesburg, South Africa
Latros International
🇿🇦Bloemfontein, South Africa
St Augustine's Hospital
🇿🇦Durban, South Africa
Sahlgrenska University Hospital Njurmottagningen
🇸🇪Goteborg, Sweden
Research Offices (5th Floor)
🇬🇧Coventry, United Kingdom
Medi-Clinic Heart Hospital (Pretoria Heart Hospital)
🇿🇦Pretoria, South Africa
A+ Science City site
🇸🇪Stockholm, Sweden
Doncaster Royal Infirmary
🇬🇧Doncaster, South Yorkshire, United Kingdom
The Royal London Hospital Whitechapel
🇬🇧London, United Kingdom
Guy's and St Thomas' Foundation Trust
🇬🇧London, United Kingdom
Northern General Hospital Campus
🇬🇧Sheffield, United Kingdom
The Office of Iqbal Saeed MD, LLC
🇺🇸Huntsville, Alabama, United States
Citrus Dialysis Center
🇺🇸Covina, California, United States
California Institute of Renal Research
🇺🇸La Mesa, California, United States
American Institute of Research
🇺🇸Whittier, California, United States
North Valley Nephrology
🇺🇸Yuba, California, United States
Whittier Internal Medicine Nephrology Medical Group
🇺🇸Whittier, California, United States
Rockdale Medical Research Associates
🇺🇸Conyers, Georgia, United States
Renal Physicians of Georgia
🇺🇸Macon, Georgia, United States
Associates in Nephrology, SC
🇺🇸Evergreen Park, Illinois, United States
Research by Design, LLC
🇺🇸Evergreen Park, Illinois, United States
RenalCare Associates
🇺🇸Peoria, Illinois, United States
Investigative Clinical Research of Indiana, LLC
🇺🇸Elwood, Indiana, United States
Mountain Kidney and Hypertension Associates, PA
🇺🇸Asheville, North Carolina, United States
Trial Management Associates
🇺🇸Wilmington, North Carolina, United States
Lake Medical Research
🇺🇸Willoughby Hills, Ohio, United States
Northeast Clinical Research Center, LLC
🇺🇸Bethlehem, Pennsylvania, United States
Preferred Primary Care Physicians, Inc.
🇺🇸Uniontown, Pennsylvania, United States
Diagnostic Clinic of Houston, PA
🇺🇸Houston, Texas, United States
Nephrology Associates of Northern Virginia, Inc.
🇺🇸Fairfax, Virginia, United States
Nephrology Specialists, P.C.
🇺🇸Mechanicsville, Virginia, United States
Clinical Research Associates of Tidewater
🇺🇸Norfolk, Virginia, United States
Renal Remission & Hypertension Consultants, PLLC
🇺🇸Bremerton, Washington, United States
Sound Medical Research
🇺🇸Port Orchard, Washington, United States
Renal Remission and Hypertension Clinic
🇺🇸Silverdale, Washington, United States
Alliance Against Diabetes
🇺🇸Las Vegas, Nevada, United States
Clinical Research Consortium
🇺🇸Las Vegas, Nevada, United States
Renal Associates, PA
🇺🇸San Antonio, Texas, United States
San Antonio Kidney Disease Center Physicians Group, P.L.L.C.
🇺🇸San Antonio, Texas, United States
Kansas Nephrology Research Institute, LLC
🇺🇸Wichita, Kansas, United States
Aarhus Universitetshospital (Aarhus Sygehus)
🇩🇰Aarhus, Denmark
Rigshospitalet
🇩🇰Copenhagen Oe, Denmark
Steno Diabetes Center
🇩🇰Gentofte, Denmark
Akademiska Sjukhuset
🇸🇪Uppsala, Sweden
Intercare Parow Medical and Dental Centre
🇿🇦Parow, South Africa
Central Texas Kidney Associates
🇺🇸Austin, Texas, United States
Capital Nephrology Clinical Research
🇺🇸Sacramento, California, United States
SMG-SNU Boramae Medical Center
🇰🇷Seoul, Korea, Republic of
Clinical Research Consultants, LLC
🇺🇸Kansas City, Missouri, United States
Miedzyleski Szpital Specjalistyczny w Warszawie
🇵🇱Warsaw, Poland
Riverside Clinical Research
🇺🇸Edgewater, Florida, United States
Shrushrut Clinical Research Association
🇮🇳Ahmedabad, Gujarat, India
Palm Springs Research Institute
🇺🇸Hialeah, Florida, United States
Nebraska Nephrology Research Institute, LLC - Research Management, Inc.
🇺🇸Lincoln, Nebraska, United States
Centre de Dialyse de Bois de Boulogne
🇨🇦Montreal, Quebec, Canada
Hopital de Sacre Coeur de Montreal
🇨🇦Montreal, Quebec, Canada
Boise Kidney and Hypertension Institute
🇺🇸Meridian, Idaho, United States
Centre de sante et de services sociaux champlain-Charles-Le Moyne
🇨🇦Greenfield Park, Quebec, Canada
Hospital Central Dr Ignacio Morones Prieto Unidad Regional de Osteoporosis
🇲🇽San Luis Potosi, San Luis, Mexico
Sheldon M Chumir Health Centre
🇨🇦Calgary, Alberta, Canada
Saskatoon Nephrology Group
🇨🇦Saskatoon, Saskatchewan, Canada
Entralogix Clincal Research Inc.
🇨🇦Brampton, Ontario, Canada
Hospital Pulau Pinang
🇲🇾George Town, Pulau Pinang, Malaysia
Comite Mexicano para la Prevencion de la Osteoporosis, A.C.
🇲🇽Mexico, DF, Mexico
Clinical Center of Serbia Institute for Endocrinology, Diabetes and Metabolic Diseases
🇷🇸Belgrade, Serbia
Universiti Sains Malaysia
🇲🇾Kota Bharu, Kelantan, Malaysia
Samsung Medical Center/Division of Nephrology
🇰🇷Seoul, Korea, Republic of
Clinical Trial Pharmacy
🇰🇷Seongnam-si, Korea, Republic of
Clinical Research Centre, Hospital Pulau Pinang
🇲🇾George Town, Pulau Pinang, Malaysia
Clinical Hospital Center "Zvezdara"
🇷🇸Belgrade, Serbia
Fakultna nemocnica s poliklinikou J.A.Reimana Presov
🇸🇰Presov, Slovakia
Boramae Medical Center/Division of Nephrology
🇰🇷Seoul, Korea, Republic of
AKDHC Medical Research Services, LLC*
🇺🇸Glendale, Arizona, United States
Samodzielny Publiczny Szpital Kliniczny im Andrzeja Mieleckiego
🇵🇱Katowice, Poland
Centrum Medyczne OSTEOMED NZOZ; Lecznica Specjalistaw
🇵🇱Warszawa, Poland
King Edward Memorial Hospital
🇮🇳Pune, Maharashtra, India
Samsung Medical Center, Department of Pharmacy
🇰🇷Seoul, Korea, Republic of
Seoul National University Bundang Hospital
🇰🇷Seongnam-si, Gyeonggi-do, Korea, Republic of
Unit Kajian Klinikal, Hospital Universiti Sains Malaysia
🇲🇾Kubang Kerian, Kelantan, Malaysia
Hospital Angeles del Pedregal
🇲🇽Angeles Del Pedregal Cp., Mexico
Centrum Medyczne "OSTEOMED" NZOZ
🇵🇱Warszawa, Poland
Clinical Center of Serbia
🇷🇸Belgrade, Serbia
ICLE SC
🇲🇽Guadalajara, Jalisco, Mexico
Jacobi Medical Center - Department of Medicine - Nephrology
🇺🇸Bronx, New York, United States
Research Management, Inc.
🇺🇸Austin, Texas, United States
Hospital Taiping
🇲🇾Taiping, Perak, Malaysia
University of Edinburgh
🇬🇧Edinburgh, United Kingdom
Division of Nephrology, Dept. of Medicine
ðŸ‡ðŸ‡°Pokfulam, Hong Kong
Queen Mary Hospital
ðŸ‡ðŸ‡°Hong Kong, Hong Kong
ICON Clinical Research
ðŸ‡ðŸ‡°Quarry Bay, Hong Kong
Division of Nephrology
ðŸ‡ðŸ‡°Pokfulam, Hong Kong
Prince of Wales Hospital
ðŸ‡ðŸ‡°Shatin, Hong Kong